Cyclic nucleotide phosphodiesterase (PDE) (PDE)

Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes that regulate the intracellular levels of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by catalyzing their hydrolysis into inactive 5'-monophosphates (nih.gov, 1.1.3). The PDE superfamily consists of 11 distinct families (PDE1–PDE11), which are classified based on their amino acid sequences, substrate specificities, and regulatory mechanisms (wikipedia.org, 1.2.3). These enzymes are ubiquitously expressed but show distinct tissue and subcellular distributions, allowing for the compartmentalized control of cyclic nucleotide signaling pathways that govern processes such as smooth muscle contraction, immune response, and synaptic plasticity (nih.gov, 1.2.4; unc.edu, 1.2.5). Dysregulation of specific PDE isoforms is associated with a wide range of diseases, including erectile dysfunction, pulmonary arterial hypertension, chronic obstructive pulmonary disease (COPD), and inflammatory conditions like psoriasis (nih.gov, 1.1.2; frontiersin.org, 1.4.4). Pharmacological intervention typically involves the use of selective inhibitors, such as PDE5 inhibitors (e.g., sildenafil) for vascular disorders and PDE4 inhibitors (e.g., roflumilast) for respiratory and inflammatory diseases (nih.gov, 1.3.1). While these drugs are clinically effective, achieving high isoform selectivity remains a challenge to avoid adverse effects like gastrointestinal distress, hypotension, and visual disturbances caused by off-target inhibition (nih.gov, 1.4.5; frontiersin.org, 1.4.4).

Other names

Phosphodiesterase, multiple isoforms3',5'-cyclic nucleotide phosphodiesterasePhosphoric diester hydrolaseCyclic nucleotide PDEPDEase

Inhibition of the catalytic hydrolysis of 3',5'-cyclic nucleotides (cAMP and cGMP), leading to increased intracellular concentrations of these second messengers and subsequent activation of downstream effectors such as protein kinase A (PKA) and protein kinase G (PKG) (nih.gov, 1.1.2; wikipedia.org, 1.2.3).